Transplants between immunologically incompatible individuals (called xenografts when the donor and recipient or host are of different species or allografts when the donor and recipient are of the same species) normally induce an immune response in the recipient individual. The immune response often leads to rejection or destruction of the transplant or, if the transplant contains immunocompetent cells, to graft-versus-host disease (GVHD).
Various techniques have been used in an attempt to reduce or eliminate the immunogenicity of transplants. For instance, transplants have been manipulated by culturing under conditions that cause selective elimination or deactivation of cells that stimulate the immune response or by treating the transplant with antisera that recognize receptors on such cells as disclosed in Transplantation Proceedings (1982) 14(4):714-723. Pancreatic islets have also been placed in semipermeable polymeric containers, called "diffusion pouches" in attempts to make an artificial pancreas as described in Diabetes (1977) 26:1136-9 and Trans.Am.Soc.Artif.Intern.Organs. (1979) 25:74-76. Biological objects have also been passively trapped in a gel which has no affinity for the living biological object tissue. The gel layer must necessarily be thick in order to completely surround the biological object.
U.S. Pat. No. 4,663,286 (Tsang et al.) discloses a gel system wherein viable cells are encapsulated using an alginate polymer. The gel layer is subsequently cross-linked with a polycationic polymer such as polylysine. A second membrane layer can be formed by contacting the capsules with a second polycationic polymer, such as polyornithine solution, or by exposure to a more highly charged density polymer such as polyvinyl amine. The second layer can, in turn be coated with alginate.
U.S. Pat. Nos. 4,806,355, 4,689,293, and 4,673,566 to Goosen et al., describe the microencapsulation of islets in a hydrogel for subsequent transplantation. The microcapsules are composed of an alginate first layer which is crossed-linked using a polyamino acid such as polylysine. Finally, a second outer, negatively charged gel layer is present and is preferably composed of sodium alginate.
U.S. Pat. Nos. 4,409,331, 4,407,957, 4,391,909 and 4,352,883 to Lim and U.S. Pat. Nos. 4,749,620 and 4,744,933 to Rha et al., variously describe methods of encapsulating biological material using a membrane formed by the interaction of an anionic polymer, such as alginate, with a cationic polymer such as polylysine.
U.S. Pat. No. 4,803,168 to Jarvis describes a cell-containing capsule composed of a glycopolysaccharide first layer and a polyanionic polymer second (outer) layer.
U.S Pat. No. 4,778,749 to Vasington et al, is directed to methods for entrapping biological material in an alkali earth metal alginate. No additional ionic layers are present.
U.S. Pat. No. 4,647,539 to Mosbach et al., pertains to the immobilization of biological material by encapsulation in polymer beads. Encapsulation is accomplished by adding the biomaterial to an aqueous polymer solution such as an agar or agarose mixture. The biomaterial/polymer solution is then dispersed in a water-insoluble dispersion medium of oil such as soybean oil, and the agar is allowed to gel.
Nilsson et al., Nature. (1983) 302:629-630, describe the encapsulation of animal cells in agarose beads formed by cooling a cell-agarose suspension in oil.
U.S Pat. No. 4,696,286 to Cochrum which is herein incorporated by reference in its entirety describes the preparation of transplants for transplantation into immunologically incompatible individuals. The transplant is coated with an immunological barrier membrane that conforms to the surface of the transplant. The membrane comprises a non-cytotoxic first layer that is bonded chemically to the surface of the transplant and a second (outer) biologically compatible, water-insoluble semipermeable layer bonded chemically to the first layer.
A difficulty that may occur in the application of the above described method is that the first layer will only bond chemically with cell surface molecules found on living tissue. Therefore, biological objects that have dead tissue clinging to their surface only receive a partial capsule.